ALPHA(2)-ADRENOCEPTOR ACTIVATION MAY TRIGGER THE INCREASED PRODUCTIONOF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN SKELETAL-MUSCLE DURING ACUTE HEMORRHAGE

Our previous studies indicated that acute haemorrhage leads to a prono unced increase in the release of endothelium-derived nitric oxide (EDN O) graded in relation to the magnitude of the blood loss. The EDNO-ind uced vasodilatation, confined selectively to the arterial 'feeder' ves sels, attenuates the concomitant reflex adrenergic constriction and th ereby prevents deleterious reduction of blood flow. The present study aimed at investigating whether the reflex release of blood-borne catec holamines might trigger this EDNO release via activation of endothelia l alpha(2)-adrenoceptors. The study was performed on the sympathectomi zed vascular bed of cat skeletal muscle with a technique permitting qu antitative recordings of resistance (tone) in consecutive vascular sec tions. Selective alpha(2)-adrenoceptor blockade with idazoxan applied at steady state vasoconstriction after a 35% blood loss evoked an init ial generalized dilator response (attributable to inhibition of post-s ynaptic smooth muscle alpha(2)-adrenoceptors), followed by a constrict or response selectively in the arterial feeder vessels, the latter com patible with the hypothesis of reduced EDNO release by alpha(2)-adreno ceptor blockade. More direct evidence for the hypothesis was obtained from studies of the vascular response to EDNO blockade (L-NAME) after haemorrhage in the presence and absence of alpha(2)-adrenoceptor block ade. The constrictor response to EDNO blockade, which is a measure of the pre-existing EDNO dilator influence (EDNO production), was signifi cantly smaller (P < 0.01) in the presence than absence of alpha(2)-adr enoceptor blockade. The results indicate that blood-borne catecholamin es, via activation of endothelial alpha(2)-adrenoceptors, trigger the increase in the EDNO release in acute haemorrhage, implying a function ally important negative feedback in the integrated control of vascular tone in bleeding.